PROJECT SUMMARY This project will develop, implement, and evaluate a transformative virtual initiative, high-impact initiative for protecting rural drug-using populations at risk from HIV/HCV outbreaks in the midst of the opioid epidemic in the United States. Most counties at high risk for HIV/HCV outbreaks are clustered in Appalachia and the Midwest. Although the origins of the opioid crisis are complex, social determinants of health, misconceptions about opioids, and a culture of isolation and despair are among the most critical causes. However, Internet use is common among opioid users in these areas (e.g., Facebook, Google) and may support scalable programs to supplement medical and public health responses to the crisis in difficult to reach regions. This project will involve two innovative platform modules: Social Action (virtual meeting and networking, contact with health officials, community consultation, and strategic news releases); and Communication (messages debunking misconceptions; messages promoting HIV/HCV testing, syringe exchange, and HIV pre-exposure prophylaxis (PrEP); on-the-spot responses to questions posed via live chat). The digital platform will incorporate Big Data methods to identify efficacious messages, misconceptions, and debunking messages. The project will target rural millennials (ages 18-35), a population that is sufficiently young to be malleable, to prevent opioid addiction and negative health outcomes in middle age. Thus, this project aligns with the NIDA agenda of generating rapid, scalable, and socially supported responses to the opioid epidemic. To evaluate the initiative, the Principal Investigator (PI) and colleagues will conduct a cluster randomized controlled trial with opioid using participants (n = 1,200) and non-opioid-using community members (n = 1,200). Assessments will occur every four months over a year. Trial outcomes will include HIV/HCV testing, syringe exchange participation, condom use, exchanging sex for money or drugs, initiation of PrEP, medication-assisted substance abuse treatment, and measures to avoid drug-related adverse events (e.g., carrying Naloxone kits for reversing overdoses), in addition to isolation and stigma measures. The Annenberg Public Policy Center has committed to hosting and maintaining the platform in parallel with www.FactCheck.org, ensuring sustainability. Given the lack of a similar social action platform in any domain and the urgent need for innovative and cost-effective approaches for the largely rural, white, poor, and anti-syringe-exchange counties at risk for HIV/HCV outbreaks, this project exemplifies the vision of the Avant-Garde Program. The PI has a distinguished record of novel, complex, theoretically-informed, and successful research on behavior change, HIV, and digital communication. The institutional support for this project is outstanding and includes www.thegrov.org, a coalition to reduce opioid vulnerability co-directed by the PI. The project brings together stellar and committed investigators at eleven elite universities and an impressive network of state health departments.